This is a request for an ADAMHA Research Scientist Development Award Level II. The overall objective of the research to define at the cellular and molecular levels the effects of ethanol on the immune system. The model systems will stress cell-mediated immunity and the interaction of the T- cell with other cells in the development of specific immune responses. The effects of ethanol on immunity will be studied in a mouse model of ad libitum ethanol ingestion by adult animals. Similarly, a model of prenatal ethanol exposure will be used in collaboration with investigators at the University of British Columbia (Dr. Joanne Weinberg). The proposed areas of investigation include the effects of ethanol on lymphocyte subpopulations, lymphocyte function by measuring proliferative responses to T- and B-cell mitogens and the production and utilization by the T- and B- cell of lymphokines. The studies will not only address the defects in T- cell function but also alterations in cellular interactions and/or factor production that lead to suppression of primary and secondary T-dependent antibody responses. Of particular importance will be the studies designed to examine the effects of ethanol on host defenses in animal models of obligate and facultative intracellular bacteria and a respiratory virus. It is hypothesized that ethanol on the infection of the fetus with this virus. It is hypothesized that ethanol will compromise the mother to such an extent that a more severe maternal infection will involve the fetus. Finally, it is proposed that the models of prenatal ethanol exposure will be established in the laboratory of the Principal Investigator during the duration of this award. This award will allow the Principal Investigator to focus a great deal of his attention on the development of these model systems as well as to establish collaborations with investigators in other disciplines to investigate the effects of ethanol on well-defined immunological and infectious disease systems. A more concerted effort by the Principal Investigator will enhance his research background in alcohol research, especially the development of relevant animal model systems, thereby accelerating his career in this field. His career at UTMB and nationally will be directly reflective of this increased effort and his ability to attract quality students and programs will develop in parallel.